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Autophagy Inhibition Enhances Apoptosis Induced by Ginsenoside Rk1 in Hepatocellular Carcinoma Cells
KO, Hyeonseok,KIM, Young-Joo,PARK, Jin-Soo,PARK, Jeong Hill,YANG, Hyun Ok Japan Society for Bioscience, Biotechnology, and A 2009 Bioscience, Biotechnology, and Biochemistry Vol.73 No.10
<P>Our previous study indicated that ginsenoside Rk1 has anti-tumor activity and that its mode of action in HepG2 cells treated for 48 h involves coordinated inhibition of telomerase and induction of apoptosis. In the present study, we found that Rk1 induces both G<SUB>1</SUB> phase arrest and autophagy, but not apoptosis, at an earlier stage of treatment. A 24-h incubation of HepG2cells with Rk1 induced G<SUB>1</SUB> phase arrest. Rk1-induced autophagy was documented by the conversion of microtubule associated protein light chain 3 (LC3)-I to LC3-II, an autophagosome marker, and monodansylcadaverine (MDC) incorporation into autolysosomes. Combination of Rk1 with an autophagy inhibitor, such as bafilomycin A1 or beclin 1 siRNA, enhanced the anti-tumor effect of Rk1. These results imply that autophagy functions as a survival mechanism in HepG2 cells against Rk1-induced apoptosis. Taken together, our results support the use of autophagy inhibitors in combination with Rk1 as an effective anti-cancer regimen in HepG2 cells.</P>
Ko, Hyeonseok,Kim, Young‐,Joo,Amor, Evangeline C.,Lee, Jong Wha,Kim, Han‐,Cheon,Kim, Hee Ju,Yang, Hyun Ok Wiley Subscription Services, Inc., A Wiley Company 2011 Journal of cellular biochemistry Vol.112 No.9
<P><B>Abstract</B></P><P>Dimethyl cardamonin (2′,4′‐dihydroxy‐6′‐methoxy‐3′,5′‐dimethylchalcone; DMC) is a naturally occurring chalcone, and it is the major compound isolated from the leaves of <I>Syzygium samarangense</I> (Blume) Merr. & L.M. Perry (Myrtaceae). Experiments were conducted to determine the effects of DMC on cell proliferation, cell‐cycle distribution, and programmed cell death in cultures of human colorectal carcinoma HCT116 and LOVO cells. Results showed that DMC inhibited HCT116 and LOVO cell proliferation and induced G<SUB>2</SUB>/M cell cycle arrest, which was associated with the conversion of microtubule associated protein light chain 3 (LC3)‐I–LC3‐II, an autophagosome marker, and the incorporation of monodansylcadaverine (MDC), a marker for the acidic compartment of autolysosomes or acidic vesicular organelles. The treatment of HCT116 and LOVO cells using a combination of DMC with an autophagy inhibitor, such as 3‐methyladenine (3‐MA), beclin 1 siRNA, or atg5 siRNA, suppressed the effect of DMC‐mediated anti‐proliferation. These results imply that DMC can suppress colorectal carcinoma HCT116 and LOVO cell proliferation through a G<SUB>2</SUB>/M phase cell‐cycle delay, and can induce autophagy, the hallmark of Type II programmed cell death (PCD). Taken together, our results suggest that DMC may be an effective chemotherapeutic agent for HCT116 and LOVO colorectal carcinoma cells. J. Cell. Biochem. 112: 2471–2479, 2011. © 2011 Wiley‐Liss, Inc.</P>
( Hyeonseok Ko ),( Sun-joong Kim ),( So Hee Shim ),( Hyoihl Chang ),( Chang Hoon Ha ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5
Shikonin, which derives from Lithospermum erythrorhizon, has been traditionally used against a variety of diseases, including cancer, in Eastern Asia. Here we determined that shikonin inhibits proliferation of gastric cancer cells by inducing apoptosis. Shikonin’s biological activity was validated by observing cell viability, caspase 3 activity, reactive oxygen species (ROS) generation, and apoptotic marker expressions in AGS stomach cancer cells. The concentration range of shikonin was 35-250 nM with the incubation time of 6 h. Protein levels of Nrf2 and p53 were evaluated by western blotting and confirmed by real-time PCR. Our results revealed that shikonin induced the generation of ROS as well as caspase 3-dependent apoptosis. c-Jun-N-terminal kinases (JNK) activity was significantly elevated in shikonin-treated cells, thereby linking JNK to apoptosis. Furthermore, our results revealed that shikonin induced p53 expression but repressed Nrf2 expression. Moreover, our results suggested that there may be a co-regulation between p53 and Nrf2, in which transfection with siNrf2 induced the p53 expression. We demonstrated for the first time that shikonin activated cell apoptosis in AGS cells via caspase 3- and JNK-dependent pathways, as well as through the p53-Nrf2 mediated signal pathway. Our study validates in partly the contribution of shikonin as a new therapeutic approaches/ agent for cancer chemotherapy.
Ko, Hyeonseok,Kim, Sun-Joong,Shim, So Hee,Chang, HyoIhl,Ha, Chang Hoon The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5
Shikonin, which derives from Lithospermum erythrorhizon, has been traditionally used against a variety of diseases, including cancer, in Eastern Asia. Here we determined that shikonin inhibits proliferation of gastric cancer cells by inducing apoptosis. Shikonin's biological activity was validated by observing cell viability, caspase 3 activity, reactive oxygen species (ROS) generation, and apoptotic marker expressions in AGS stomach cancer cells. The concentration range of shikonin was 35-250 nM with the incubation time of 6 h. Protein levels of Nrf2 and p53 were evaluated by western blotting and confirmed by real-time PCR. Our results revealed that shikonin induced the generation of ROS as well as caspase 3-dependent apoptosis. c-Jun-N-terminal kinases (JNK) activity was significantly elevated in shikonin-treated cells, thereby linking JNK to apoptosis. Furthermore, our results revealed that shikonin induced p53 expression but repressed Nrf2 expression. Moreover, our results suggested that there may be a co-regulation between p53 and Nrf2, in which transfection with siNrf2 induced the p53 expression. We demonstrated for the first time that shikonin activated cell apoptosis in AGS cells via caspase 3- and JNK-dependent pathways, as well as through the p53-Nrf2 mediated signal pathway. Our study validates in partly the contribution of shikonin as a new therapeutic approaches/agent for cancer chemotherapy.
Hyeonseok Kim(김현석),Young D. Suh(서영덕),Jaeho Shin(신재호),Phillip Won(원필립),Seongmin Jung(정성민),Jinhyeong Kwon(권진형),Seung Hwan Ko(고승환) 대한기계학회 2016 대한기계학회 춘추학술대회 Vol.2016 No.12
We demonstrate a novel class of flexible transparent conductor based on metal nanowire micro-bundled networks at random patterns. Original random patterns are prepared from controlled random cracking of high-stress silicon nitride on the silicon substrate, and employed as repetitively usable master molds with independently controllable pattern density and linewidth. Silver nanowires are subsequently placed in the random crack channels through a facile solution process and transferred to the polymer substrate with UV curable epoxy resin. The resultant flexible and transparent conductor, spanning over wafer scale at high reproducibility, not only exhibits enhanced mechanical robustness upon repeated bending or scratching, which often occurs when used as touch-screen panel, but also is free from the moire pattern problem due to the random nature of nanowire bundle patterns. Further application of the resultant flexible transparent conductor as a touch-screen panel confirms easy
웨어러블 전자 디바이스 응용을 위한 고 신축성, 투명 금속 나노 와이어 가열기
김현석(Hyeonseok Kim),홍석준(Sukjoon Hong),이하범(Habeom Lee),문현진(Hyunjin Moon),권진형(Jinhyeong Kwon),김동관(Dongkwan Kim),고승환(Seung Hwan Ko) 대한기계학회 2015 대한기계학회 춘추학술대회 Vol.2015 No.11
We introduce a highly stretchable and transparent electrical heater intended for future wearable applications by constructing a partially embedded silver nanowire percolative network on an elastic substrate. The Ag NW network heater proposed in this study not only exhibits superior optical transmittance and electrical conductivity comparable to ITO, but also outstanding electrical, mechanical and thermal stability withstanding 60 % strain at a temperature of 60 ℃ with high reliability and fast temporal response. The outstanding performance of Ag NW as a stretchable and transparent heater is attributed to the unique microscopic morphology of the Ag NW at the interface, which also enables easy manipulation of its spatial temperature profile through direct patterning of the Ag NW by a selective laser ablation process. The stable operation of Ag NW network heater on human wrists under real-time compressive/tensile strain, bending and twisting further proves its high potential for lightweight, biocompatible and versatile wearable applications.
Yoon, Hyeonseok,Ko, Sungrok,Jang, Jyongsik Royal Society of Chemistry 2007 Chemical communications Vol.2007 No.14
<P>Palladium nanoparticles were deposited with high dispersion and stability on nitrogen-doped magnetic carbon nanoparticles by a simple impregnation method, and their catalytic performance was investigated for Heck, Suzuki, and Sonogashira coupling reactions.</P> <P>Graphic Abstract</P><P>Palladium nanoparticles were deposited with high dispersion and stability on nitrogen-doped magnetic carbon nanoparticles by a simple impregnation method, and their catalytic performance was investigated for Heck, Suzuki, and Sonogashira coupling reactions. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b616660a'> </P>
Lee, Dahae,Ko, Hyeonseok,Kim, Young-Joo,Kim, Su-Nam,Choi, Kyung-Chul,Yamabe, Noriko,Kim, Ki Hyun,Kang, Ki Sung,Kim, Hyun Young,Shibamoto, Takayuki American Chemical Society 2016 Journal of agricultural and food chemistry Vol.64 No.4
<P>The effects of a red raspberry component, sanguiin H-6 (SH-6), on the induction of apoptosis and the related signaling pathways in A2780 human ovarian carcinoma cells were investigated. SH-6 caused an antiproliferative effect and a severe morphological change resembling that of apoptotic cell death but no effect on the cancer cell cycle arrest: In addition, SH-6 induced an early apoptotic effect and activation of caspases as well as the deavage of PARP, which is a hallmark of apoptosis. The early apoptotic percentages of A2780 cells exposed to 20 and 40 mu M SH-6 were 35.39 and 41.76, respectively. Also, SH-6 caused the activation of mitogen-activated protein, kinases (MAPKs), especially p38, and the increase of truncated p15/BID. These results in the present study suggest that the apoptosis of A2780 human ovarian carcinoma cells by SH-6 is mediated by the MAPK p38 and a caspase-8-dependent BID cleavage pathway.</P>